This application is a national stage filing of PCT International Application No. PCT/FI99/00540, filed on Jun. 18, 1999, which published in the English language.
The present invention relates to the use of levosimendan, or (xe2x88x92)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile (I), or pharmaceutically acceptable salts thereof in the manufacture of a medicament for the treatment of pulmonary hypertension.
Levosimendan, which is the (xe2x88x92)-enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, and the method for its preparation is described in EP 565546 B1. Levosimendan is potent in the treatment of heart failure and has significant calcium dependent binding to troponin. Levosimendan is represented by the formula: 
The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 1061-1066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S63-S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients.
Pulmonary hypertension is classified clinically as either primary of secondary. Primary pulmonary hypertension, the cause of which is as yet unknown, is diagnosed only after all secondary causes, such as pulmonary emboli, of increased pulmonary pressure are excluded.
At the moment there is no successful cure for pulmonary hypertension. Administration of vasodilatating drugs has not proved to be useful in patients suffering from pulmonary hypertension. The prognosis is poor, with a median survival time of about 2 years.
It has now been found that levosimendan is useful in the treatment of pulmonary hypertension.
Therefore, the present invention provides the use of (xe2x88x92)-[[4-(1,4,5,6-tetra-hydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of pulmonary hypertension.
The present invention also provides a method for the treatment of pulmonary hypertension in a patient, said method comprising administering to a patient in need thereof a pulmonary blood pressure lowering amount of (xe2x88x92)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof.